Antibody conjugates, in which antibodies are covalently attached to reporter or effector groups, have been used in diagnosis, and, to a more limited extent, in therapy. The antibody is generally selected on the basis of its affinity and specificity for a particular target antigen, such that, in use, it should be able to deliver the reporter of effector group to a desired site and maintain it there for a length of time.
Bispecific heterodimeric antibodies have been previously described in which Fab' fragments have been joined via a thioether linkage [Glennie M. J. et al J. Immunol. 139, 2367, (1987)]. Antibodies in which the fluorescein derivative crabescein has been linked across a disulphide bond have also been described [Packard, B. P. et al, Biochemistry 25, 3548 (1986)].
We have now found that by cross-linking at least two chains of an antibody in a cross-linkage away from the antigen binding domains the binding capacity of the modified antibody may be advantageously enhanced relative to the unmodified antibody. In vivo, modified antibodies of this type also have good blood clearance and, in the presence of a tumour, give advantageously high tumours; blood and tumour: bone ratios. Such antibodies, when labelled with a reporter or effector group thus offer potential advantages over conventional labelled antibodies.